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Autologous tumor vaccine modified with nonlytic Newcastle disease virus (ATV-NDV) is a promising vaccine for cancer immunotherapy. IL-7 plays a critical role in lymphocyte development and homeostasis. To improve the efficacy of ATV-NDV, we inserted the murine IL-7 gene into the genome of nonlytic NDV strain LX using reverse genetic system. The insertion of the IL-7 gene neither affected the main features of NDV replication nor its tumor selectivity. The gene product was biologically active and stable. Then we tested the antitumor effects of the autologous tumor vaccine modified with LX/(IL-7) in the murine tumor models. We showed that tumor cells modified with LX/IL-7 induced a strong antitumor activity both in prophylaxis and therapeutic models. The IFN-γ production and the cytotoxicity of tumor-specific CD8+ T cells were significantly enhanced after immunization with tumor cells modified with LX/(IL-7) in both models. Although the tumor-infiltrating CD4+ T cells and CD8+ T cells were both increased and their IFN-γ productions also were upregulated, the antitumor activity of the tumor vaccine modified with LX/(IL-7) was dependent on CD8+ T cells. Our results demonstrated that the autologous tumor vaccine modified with NDV strain LX/(IL-7) could promote the antitumor immune responses mediated by CD8+ T cells and significantly improve the efficacy of the ATV-NDV.

The new-emerging PRV variants plague the vaccinated pigs and caused huge economic loss to local pig industry in China since 2011. The current commercial PRV vaccines cannot provide complete protection as the new-emerging PRV variants are antigenically different from the classical viruses. It is urgent to develop more safe and effective PRV vaccines based on the current circulating field isolates. In this study, a gE gene-deleted PRV based on the PRV HN1201, a representative PRV variant, was generated and the efficacy was tested on 3-week-old pigs in the form of killed vaccine. After fatal PRV HN1201 challenge, all vaccinated pigs survived without showing any clinical symptoms, but all unvaccinated pigs exhibited pseudorabies-specific respiratory and neurological signs with 100% mortality rate within 6 days after infection. The vaccinated pigs developed high level of gB and neutralizing antibodies after vaccination which may correlate to the protection provided by vaccine. Therefore, this gE gene-deleted PRV could be a promising vaccine candidate for the control of currently epidemic pseudorabies in China.

In China, the re-emerging pseudorabies virus (PRV) variant has caused large-scale outbreaks of pseudorabies in swine herds with classical PRV vaccine immunization since late 2011. Here, a recombinant PRV with TK/gI/gE/11k/28k deletion was constructed based on variant HN1201 strain isolated in 2012, by the bacterial artificial chromosome infectious clones. Compared with the parental virus, the recombinant PRV rHN1201TK−/gE−/gI−/11k−/28k− showed a similar virus grown curve and exhibited smaller plaques. The vaccination of rHN1201TK−/gE−/gI−/11k−/28k− could elicit an earlier and higher level of gB antibody, and the neutralizing antibodies elicited by rHN1201TK−/gE−/gI−/11k−/28k− were effective against both PRV classical and variant strains. Clinically, the body temperature of the pigs immunized with rHN1201TK−/gE−/gI−/11k−/28k− was significantly lower than that of the classical PRV vaccine immunized pigs, and the recombinant PRV could provide effective protection against the challenge with the PRV variant. These results imply that the rHN1201TK−/gE−/gI−/11k−/28k− could be a promising vaccine candidate for the prevention of the current epidemic of pseudorabies in China.

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